A 3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn

Ryuji Terayama, Mitsuyasu Tabata, Kotaro Maruhama, Seiji Iida

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Peripheral nerve injuries cause glial activation and neuronal hyperactivity in the spinal dorsal horn. These changes have been considered to be involved in the underlying mechanisms for the development and maintenance of neuropathic pain. Using double immunofluorescence labeling, we previously demonstrated that spinal microglial activation induced by nerve injury enhanced convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents. The adenosine A 3 receptor (A 3 AR) agonists have been shown to have antinociceptive activities in several experimental neuropathic pain models. However, the mechanisms underlying these antinociceptive actions of the A 3 AR agonist are still not fully explored. In this study, the effects of the A 3 AR agonist (i.e., IB-MECA) on microglial activation, enhancement of convergent nociceptive inputs, and nocifensive behaviors were examined after tibial nerve injury. Injury to the tibial nerve initially caused hyposensitivity to touch stimulus at 3 days, and then resulted in tactile allodynia at 14-day post-injury. The daily systemic administration of IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury or 7 days after nerve injury prevented the development of behaviorally assessed hypersensitivities, and spinal microglial activation induced by nerve injury. These treatments also suppressed anomalous convergence of nociceptive primary inputs in the spinal dorsal horn. The present findings indicate that the A 3 AR agonist attenuates neuropathic pain states by suppressing enhanced microglial activation, and anomalous convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents after injury to the peripheral nerve.

Original languageEnglish
Pages (from-to)3203-3213
Number of pages11
JournalExperimental Brain Research
Volume236
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

Keywords

  • A AR
  • Adenosine
  • Microglia
  • Nerve injury
  • Spinal dorsal horn

ASJC Scopus subject areas

  • Neuroscience(all)

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